“Animals like amphioxus live in huge populations where the rare mutants with rearranged chromosomes are at a disadvantage and typically die out, whereas, in small, subdivided populations, which is more typical of mammals, rearrangements are more likely to survive and spread. That’s one hypothesis,” said Rokhsar.
Vertebrates mixed it up
Alternatively, there may be some unknown reason why sets of genes have to remain together. One famous example is the Hox genes, which determine which end of the animal embryo forms the head and which the tail, and all gradations in between. These genes are all clustered together on one chromosome in most invertebrates, and this clustering is important for their deployment during development. The functional clustering of these genes may be an exception, however, and there’s no evidence yet that the clusters found in the recent study are functionally related, Rokhsar said.
The simple conservation of chromosomes stops with invertebrates, because early in vertebrate evolution, the entire genome was duplicated twice in the lineage leading to jawed vertebrates, a group that includes mammals, birds, reptiles, amphibians and most fish. During the course of these large-scale duplications, a series of chromosomal reorganizations forged the genomes of the earliest jawed vertebrates, which eventually gave rise to humans. By tracking groups of genes as they moved from one chromosome to another as the earliest vertebrates evolved, however, Rokhsar and collaborators were able to leap over the vertebrate-invertebrate divide and connect the earliest animal chromosomes with those of contemporary vertebrates.
“One of the cool things is that once we infer these ancient proto-chromosomes and organize them on the tree of life, then we can make predictions. If you go and sequence some other genomes, we predict that you will inevitably find that these genes are mixed together on the same chromosome,” he said. “Unlike physics or chemistry, you don’t usually get to make such predictions in biology. But now we know something, in a sense, about almost all animal genomes from this comparison.”
The work was supported by the National Institutes of Health (RO1 HD080708), the Chan Zuckerberg Biohub, and the Molecular Genetics Unit of the Okinawa Institute of Science and Technology Graduate University (OIST) in Japan, where Rokhsar has a joint appointment as a visiting professor.
Other co-authors of the paper are Jessen Bredeson, Kodiak Berkoff and Therese Mitros of UC Berkeley; Ferdinand Marletaz of OIST and University College in the U.K.; Darrin Schultz of UC Santa Cruz and the Monterey Bay Aquarium Research Institute; Brendan O’Connell and Richard Green of UC Santa Cruz; the late Paul Dear of Mote Research Ltd. in the U.K.; Daniel Martinez of Pomona College; Robert Steele of UC Irvine; and Charles David of the Ludwig Maximilian University of Munich in Germany.
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